The goal of this brain imaging study is to examine brain connectivity in adolescent girls with non-suicidal self- injury (NSSI). To date, little is knwn about the neurobiological underpinnings of NSSI. This behavior occurs in a wide range of conditions including major depressive disorder (MDD), borderline personality disorder (BPD), anxiety disorders, substance abuse disorders, adjustment disorders and eating disorders. Conversely, many adolescents with NSSI do not meet criteria for any psychiatric disorders. Thus, the field has begun to consider NSSI not as a symptom of a specific disorder, but as an entity in its own right. Our laboratory has been developing methods to examine the connections within brain networks (connectivity) using diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). These tools allow for the application of systems-based approaches to examining the neural underpinnings of psychopathology, a recent priority in the field. Thus, instead of examining specific brain regions, recent research has been focused on characterizing connectivity within neural circuitry. Examination of brain connectivity is particularly relevant to studying problems that emerge in adolescence given the ongoing maturation of connections within relevant brain systems during this time period. The hypothesis of the current study is that aberrant neural circuitry underlies the tendency to engage in NSSI in adolescents. As we examine brain connectivity in this group, we will explore key psychological dimensions such as emotion regulation (and others) that could mediate the link between circuitry abnormalities and NSSI. In keeping with the NIH initiative RDoC, we focus not on diagnosis but on a specific behavior (i.e., NSSI); to increase homogeneity of the NSSI group we will include several constraints: medication-naive, girls only, a narrow range of age and pubertal development, and no history of SA. This project may represent the first study to examine neural circuitry of NSSI in adolescents, and thus will be a major step forward in uncovering neurobiological mechanisms that underlie NSSI. Elucidating the neural correlates of NSSI is especially important during adolescence; early intervention during a time of increased neuroplasticity could prevent entrenchment of aberrant behavior and promote healthy neurodevelopment. This project will provide the foundation for future longitudinal studies that will examine (a) predictors for course of psychopathology and treatment response, and (2) the impact of treatment on aberrant connectivity patterns in adolescents with NSSI (i.e., mechanisms of successful treatment.) PUBLIC HEALTH RELEVANCE: Deliberate self harm (DSH) occurs frequently in adolescents and poses considerable public health risks. Development of improved identification and treatment strategies depends on improving current understanding of underlying disease mechanisms. Results from the proposed study will yield new information to shed light on the pathophysiology of DSH in adolescence. These results will provide important guidance for future research investigating the impact of treatment on abnormal mechanisms in adolescents with DSH.